tbuckley/cabot-search huggingface dataset:
Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease
Authors: Guang-Hui Deng, Chao-Feng Wu, Yun-Jia Li, Hao Shi, Wei-Chao Zhong, Mu-Keng Hong, Jun-Jie Li, Jia-Min Zhao, Chang Liu, Meng-Chen Qin, Zhi-Yun Zeng, Wei-Min Zhang, Ken Kin Lam Yung, Zhi-Ping Lv, Lei Gao
Journal: Military Medical Research (2023)

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD. Methods Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1 -knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining. Results Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes ( P &lt; 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68 + CD163 + macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers ( P &lt; 0.05). Conclusions These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD.
Polycystic Ovary Syndrome Fuels Cardiovascular Inflammation and Aggravates Ischemic Cardiac Injury
Authors: Ling Gao, Yichao Zhao, Haiyan Wu, Xianhua Lin, Fei Guo, Jie Li, Yuhang Long, Bokang Zhou, Junsen She, Chen Zhang, Jianzhong Sheng, Li Jin, Yanting Wu, Hefeng Huang
Journal: Circulation (2023)

Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, is associated with an increased prevalence and extent of coronary artery disease. However, the mechanism through which PCOS affects cardiac health in women remains unclear.
The effectiveness of dance movement interventions for older adults with mild cognitive impairment, Alzheimer’s disease, and dementia: A systematic scoping review and meta-analysis
Authors: Dan Tao, Roger Awan-Scully, Garrett I. Ash, Zhong Pei, Yaodong Gu, Yang Gao, Alistair Cole, Julien S. Baker
Journal: Ageing Research Reviews (2023)
Lifestyle effects on aging and CVD: A spotlight on the nutrient-sensing network
Authors: Kaiying Yang, Rongyao Hou, Jie Zhao, Xia Wang, Jin Wei, Xudong Pan, Xiaoyan Zhu
Journal: Ageing Research Reviews (2023)

Aging is widespread worldwide and a significant risk factor for cardiovascular disease (CVD). Mechanisms underlying aging have attracted considerable attention in recent years. Remarkably, aging and CVD overlap in numerous ways, with deregulated nutrient sensing as a common mechanism and lifestyle as a communal modifier. Interestingly, lifestyle triggers or suppresses multiple nutrient-related signaling pathways. In this review, we first present the composition of the nutrient-sensing network (NSN) and its metabolic impact on aging and CVD. Secondly, we review how risk factors closely associated with CVD, including adverse life states such as sedentary behavior, sleep disorders, high-fat diet, and psychosocial stress, contribute to aging and CVD, with a focus on the bridging role of the NSN. Finally, we focus on the positive effects of beneficial dietary interventions, specifically dietary restriction and the Mediterranean diet, on the regulation of nutrient metabolism and the delayed effects of aging and CVD that depend on the balance of the NSN. In summary, we expound on the interaction between lifestyle, NSN, aging, and CVD.
Proteomic prediction of incident heart failure and its main subtypes
Authors: Valur Emilsson, Brynjolfur G. Jonsson, Thomas R. Austin, Valborg Gudmundsdottir, Gisli T. Axelsson, Elisabet A. Frick, Thorarinn Jonmundsson, Anna E. Steindorsdottir, Joseph Loureiro, Jennifer A. Brody, Thor Aspelund, Lenore J. Launer, Gudmundur Thorgeirsson, Kirsten A. Kortekaas, Jan H. Lindeman, Anthony P. Orth, John R. Lamb, Bruce M. Psaty, Jorge R. Kizer, Lori L. Jennings, Vilmundur Gudnason
Journal: European Journal of Heart Failure (2023)
Risk of Hypertensive Disorders and Preterm Birth in Pregnant Women With Systemic Vasculitides: A Nationwide <scp>Population‐Based</scp> Cohort Study
Authors: Camille Mettler, Nathanael Beeker, Mathis Collier, Véronique Le Guern, Benjamin Terrier, Laurent Chouchana
Journal: Arthritis & Rheumatology (2023)

Objective Even though systemic vasculitides (SVs) affect primarily patients over 50 years of age, they can occur among women of childbearing age. Preterm birth (PTB) and hypertensive disorders are frequent complications of pregnancy in SVs. This study aims to evaluate the risk of hypertensive disorders and PTB among pregnant women with SVs, and to identify associated risk factors. Method Using the French health insurance data warehouse, we conducted a nationwide cohort study including all pregnancies between 2013 and 2018 in women with SVs. Theses pregnancies were matched to pregnancies among women without SVs. We estimated risk of hypertensive disorders and PTB risk during pregnancy among women with SVs and investigated associated risk factors using a nested case‐control design. Results Among 3,155,723 pregnancies, we identified 646 pregnancies in women with SVs, matched to 3,230 controls. SVs were significantly associated with hypertensive disorders (odds ratio [OR] 1.7, 95% confidence interval [95% CI] 1.3–2.2) and PTB (OR 1.8, 95% CI 1.4–2.3). Chronic renal failure before pregnancy, history of or treated arterial hypertension, the occurrence of vasculitides flare during pregnancy, and the subgroup of SVs were independently associated with the occurrence of hypertensive disorders. Maternal age at delivery, chronic renal failure before conception, and the occurrence of vasculitides flare during pregnancy were independently associated with the occurrence of PTB. Conclusion About one of seven pregnancies in women with SVs is associated with hypertensive disorders or preterm birth. The occurrence of vasculitides flare was associated with these complications. Our findings support the importance of prepregnancy counseling to ensure disease stability. image
Insights gained from single-cell analysis of chimeric antigen receptor T-cell immunotherapy in cancer
Authors: Lu Tang, Zhong-Pei Huang, Heng Mei, Yu Hu
Journal: Military Medical Research (2023)

Abstract Advances in chimeric antigen receptor (CAR)-T cell therapy have significantly improved clinical outcomes of patients with relapsed or refractory hematologic malignancies. However, progress is still hindered as clinical benefit is only available for a fraction of patients. A lack of understanding of CAR-T cell behaviors in vivo at the single-cell level impedes their more extensive application in clinical practice. Mounting evidence suggests that single-cell sequencing techniques can help perfect the receptor design, guide gene-based T cell modification, and optimize the CAR-T manufacturing conditions, and all of them are essential for long-term immunosurveillance and more favorable clinical outcomes. The information generated by employing these methods also potentially informs our understanding of the numerous complex factors that dictate therapeutic efficacy and toxicities. In this review, we discuss the reasons why CAR-T immunotherapy fails in clinical practice and what this field has learned since the milestone of single-cell sequencing technologies. We further outline recent advances in the application of single-cell analyses in CAR-T immunotherapy. Specifically, we provide an overview of single-cell studies focusing on target antigens, CAR-transgene integration, and preclinical research and clinical applications, and then discuss how it will affect the future of CAR-T cell therapy.
Minor GPI(-) granulocyte populations in aplastic anemia and healthy individuals derived from a few PIGA-mutated hematopoietic stem progenitor cells
Authors: Hiroki Mizumaki, Dung Cao Tran, Kohei Hosokawa, Kazuyoshi Hosomichi, Yoshitaka Zaimoku, Hiroyuki Takamatsu, Hirohito Yamazaki, Ken Ishiyama, Rena Yamazaki, Hiroshi Fujiwara, Atsushi Tajima, Shinji Nakao
Journal: Blood Cancer Journal (2023)

Magnetic cell separationAfter enrichment Before enrichment FLAER 84.4% 0.087%
Neuropeptide Y is elevated in heart failure and is an independent predictor of outcomes
Authors: Kirsty McDowell, Carly Adamson, Colette Jackson, Ross Campbell, Paul Welsh, Mark C. Petrie, John J.V. McMurray, Pardeep S. Jhund, Neil Herring
Journal: European Journal of Heart Failure (2023)

Neuropeptide Y (NPY) is the most abundant neuropeptide found in the heart and is released alongside norepinephrine following prolonged sympathetic activation, a process that is implicated in the pathophysiology of heart failure (HF). In patients with severely impaired left ventricular ejection fraction (LVEF) undergoing cardiac resynchronization therapy, higher levels of NPY measured in coronary sinus blood, are associated with poorer outcome. The aim was to examine the association of peripheral venous NPY levels and outcomes in a HF population with a range of LVEF, using a highly sensitive and specific assay.
Functional Hydrogel Co‐Remolding Migration and Differentiation Microenvironment for Severe Spinal Cord Injury Repair
Authors: Dingyang Liu, He Shen, Kai Zhang, Yeyu Shen, Runlin Wen, Xinghui He, Ge Long, Xing Li
Journal: Advanced Healthcare Materials (2023)

Spinal cord injury (SCI) activates nestin
Prophylactic use of diquafosol eye drops for dupilumab‐associated conjunctivitis in patients with severe atopic dermatitis: An open‐label prospective study
Authors: Kihyuk Shin, Jin‐Su Lee, Hyeshin Jeon, Gi‐Wook Lee, Jun‐Oh Shin, Dongyoung Roh, Yeona Kim, Sang‐Hyeon Won, Jungsoo Lee, Hoon‐Soo Kim, Byung‐Soo Kim, Moon‐Bum Kim, Hyun‐Chang Ko
Journal: Allergy (2023)

The data that supports the findings of this study are available in the supplementary material of this article. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease
Authors: Maximillian A. Rogers, Francesca Bartoli-Leonard, Kang H. Zheng, Aeron M. Small, Hao Yu Chen, Cassandra L. Clift, Takaharu Asano, Shiori Kuraoka, Mark C. Blaser, Katelyn A. Perez, Pradeep Natarajan, Calvin Yeang, Erik S.G. Stroes, Sotirios Tsimikas, James C. Engert, George Thanassoulis, Christopher J. O’Donnell, Masanori Aikawa, Sasha A. Singh, Elena Aikawa
Journal: Circulation (2023)

High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake.
Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application
Authors: Xiaoxue Ren, Mingle Huang, Weixiang Weng, Yubin Xie, Yifan Wu, Shenghua Zhu, Ying Zhang, Dongming Li, Jiaming Lai, Shunli Shen, Jie Lin, Ming Kuang, Xiaoxing Li, Jun Yu, Lixia Xu
Journal: Cell Reports Medicine (2023)

Patients with biliary tract cancer (BTC) show different responses to chemotherapy, and there is no effective way to predict chemotherapeutic response. We have generated 61 BTC patient-derived organoids (PDOs) from 82 tumors (74.4%) that show similar histological and genetic characteristics to the corresponding primary BTC tissues. BTC tumor tissues with enhanced stemness- and proliferation-related gene expression by RNA sequencing can more easily form organoids. As expected, BTC PDOs show different responses to the chemotherapies of gemcitabine, cisplatin, 5-fluoruracil, oxaliplatin, etc. The drug screening results in PDOs are further validated in PDO-based xenografts and confirmed in 92.3% (12/13) of BTC patients with actual clinical response. Moreover, we have identified gene expression signatures of BTC PDOs with different drug responses and established gene expression panels to predict chemotherapy response in BTC patients. In conclusion, BTC PDO is a promising precision medicine tool for anti-cancer therapy in BTC patients.
Cover Image, Volume 43, Issue 11
Authors: Ai Zhuang, Xiang Gu, Tongxin Ge, Shaoyun Wang, Shengfang Ge, Peiwei Chai, Renbing Jia, Xianqun Fan
Journal: Cancer Communications (2023)

The cover image is based on the Original Article Targeting histone deacetylase suppresses tumor growth through eliciting METTL14-modified m6A RNA methylation in ocular melanoma by Ai Zhuang et al., https://doi.org/10.1002/cac2.12471.
MDR1-expressing CD4<sup>+</sup>T cells with Th1.17 features resist to neoadjuvant chemotherapy and are associated with breast cancer clinical response
Authors: Anthony Di Roio, Margaux Hubert, Laurie Besson, Marion Bossennec, Céline Rodriguez, Yenkel Grinberg-Bleyer, Guilhem Lalle, Lyvia Moudombi, Raphael Schneider, Cyril Degletagne, Isabelle Treilleux, Daniel J Campbell, Séverine Metzger, Thomas Duhen, Olivier Trédan, Christophe Caux, Christine Ménétrier-Caux
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Multidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets in which it confers chemoresistance. Among human T cells, MDR1 is expressed by most CD8 + T cells, and a subset of CD4 + T helper (Th) cells. Here we explored the expression, function and regulation of MDR1 on CD4 + T cells and investigated the role of this population in response to neoadjuvant chemotherapy (NAC) in BC. Methods Phenotypic and functional characteristics of MDR1 + CD4 Th cells were assessed on blood from healthy donors and patients with BC by flow cytometry. These features were extended to CD4 + Th cells from untreated breast tumor by flow cytometry and RNA-sequencing (RNA-seq). We performed in vitro polarization assays to decipher MDR1 regulation on CD4 Th cells. We evaluated in vitro the impact of chemotherapy agents on MDR1 + CD4 + Th cells. We analyzed the impact of NAC treatment on MDR1 + CD4 + Th cells from blood and tumors and their association with treatment efficacy in two independent BC cohorts and in a public RNA-seq data set of BC tumor biopsies before and after NAC. Finally, we performed single cell (sc) RNAseq of blood CD4 + memory T cells from NAC-treated patients and combined them with an scRNAseq public data set. Results MDR1 + CD4 Th cells were strongly enriched in Th1.17 polyfunctional cells but also in Th17 cells, both in blood and untreated breast tumor tissues. Mechanistically, Tumor growth factor (TGF)-β1 was required for MDR1 induction during in vitro Th17 or Th1.17 polarization. MDR1 expression conferred a selective advantage to Th1.17 and Th17 cells following paclitaxel treatment in vitro and in vivo in NAC-treated patients. scRNAseq demonstrated MDR1 association with tumor Th1.17 and Th with features of cytotoxic cells. Enrichment in MDR1 + CD4 + Th1.17 and Th17 cells, in blood and tumors positively correlated with pathological response. Absence of early modulation of Th1.17 and Th17 in NAC-resistant patients, argue for its use as a biomarker for chemotherapy regimen adjustment. Conclusion MDR1 favored the enrichment of Th1.17 and Th17 in blood and tumor after NAC that correlated to clinical response.
Elevated 68Ga-FAPI Activity in Klebsiella pneumoniae Invasion Syndrome
Authors: Yang Xie, Wenxin Tang, Jiao Ma, Yudi Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2023)

Abstract Klebsiella pneumoniae invasion syndrome is a rare disease associated with primary liver abscess and secondary extrahepatic infection. We report a case of K. pneumoniae invasion syndrome with elevated 68 Ga-FAPI uptake, mimicking malignancy with multiple metastases. Our case illustrated that K. pneumoniae invasion syndrome should be considered as a possible etiology when diagnosing multiple 68 Ga-FAPI–avid liver foci with metastatic lesions. Besides, PET/CT could be an integrated tool to search for systemic occult lesions in K. pneumoniae invasion syndrome.
Identification of eczema clusters and their association with filaggrin and atopic comorbidities: analysis of five birth cohorts
Authors: Sadia Haider, Raquel Granell, John A Curtin, John W Holloway, Sara Fontanella, Syed Hasan Arshad, Clare S Murray, Paul Cullinan, Stephen Turner, Graham Roberts, Angela Simpson, Adnan Custovic
Journal: British Journal of Dermatology (2023)

Longitudinal modelling of the presence/absence of current eczema through childhood has identified similar phenotypes, but their characteristics often differ between studies.
Cationic amino-acid functionalized polymethacrylamide vectors for siRNA transfection based on modification of poly(2-isopropenyl-2-oxazoline)
Authors: Florica Adriana Jerca, Cristina Muntean, Katrien Remaut, Valentin Victor Jerca, Koen Raemdonck, Richard Hoogenboom
Journal: Journal of Controlled Release (2023)
Public Sector Learning Health Care Systems—Improving Patient Experience, Workforce Well-Being, and Recovery Outcomes
Authors: Carlos Blanco, Robert K. Heinssen, Wendy N. Tenhula
Journal: JAMA Psychiatry (2023)

This Viewpoint discusses the need for integrating basic, clinical, and epidemiological science into behavioral health care delivery to develop more scalable and sustainable learning health care systems and improve population health and patient experience, reduce costs, and promote the well-being of the health care workforce.
Corrected to Open Access Status
Journal: JAMA Cardiology (2023)

Georgios Georgiopoulos, MD; Simon Kraler, MD; Matthias Mueller-Hennessen, MD; Dimitrios Delialis, MD; Georgios Mavraganis, MD; Kateryna Sopova, MD; Florian A. Wenzl, MD; Lorenz Räber, MD; Moritz Biener, MD; Barbara E. Stähli, MD; Eleni Maneta, MD; Luke Spray, MD; Juan F. Iglesias, MD; Jose Coelho-Lima, MD, PhD; Simon Tual-Chalot, PhD; Olivier Muller, MD, PhD; François Mach, MD; Norbert Frey, MD; Daniel Duerschmied, MD; Harald F. Langer, MD; Hugo Katus, MD; Marco Roffi, MD; Giovanni G. Camici, PhD; Christian Mueller, MD; Evangelos Giannitsis, MD; Ioakim Spyridopoulos, MD; Thomas F. Lüscher, MD; Konstantinos Stellos, MD; Kimon Stamatelopoulos, MD
Dacarbazine-primed carbon quantum dots coated with breast cancer cell-derived exosomes for improved breast cancer therapy
Authors: Pratiksha Tiwari, Ravi Prakash Shukla, Krishna Yadav, Neha Singh, Disha Marwaha, Shalini Gautam, Avijit Kumar Bakshi, Nikhil Rai, Ankit Kumar, Deepak Sharma, Prabhat Ranjan Mishra
Journal: Journal of Controlled Release (2023)
Solitary Pulmonary Fibroleiomyomatous Hamartoma on 18F-FDG PET/CT
Authors: Yi Tao, Feifei Wang, Jiao Yan, Zhengguo Chen, Chuandong He
Journal: Clinical Nuclear Medicine (2023)

Abstract Solitary pulmonary fibroleiomyomatous hamartoma is a very rare benign tumor. A 57-year-old man presented with dry cough over 1 month. A CT showed an irregular nodule in the left upper lobe of the lung. A malignant tumor was suspected, and further investigation with 18 F-FDG PET/CT showed the pulmonary nodule with slightly increased FDG uptake. Thoracoscopic resection was performed. Subsequent histopathological and immunohistochemical tests confirmed the diagnosis of fibroleiomyomatous hamartoma.
From Genotype to Phenotype: How Enhancers Control Gene Expression and Cell Identity in Hematopoiesis
Authors: Roger Mulet-Lazaro, Ruud Delwel
Journal: HemaSphere (2023)

Blood comprises a wide array of specialized cells, all of which share the same genetic information and ultimately derive from the same precursor, the hematopoietic stem cell (HSC). This diversity of phenotypes is underpinned by unique transcriptional programs gradually acquired in the process known as hematopoiesis. Spatiotemporal regulation of gene expression depends on many factors, but critical among them are enhancers—sequences of DNA that bind transcription factors and increase transcription of genes under their control. Thus, hematopoiesis involves the activation of specific enhancer repertoires in HSCs and their progeny, driving the expression of sets of genes that collectively determine morphology and function. Disruption of this tightly regulated process can have catastrophic consequences: in hematopoietic malignancies, dysregulation of transcriptional control by enhancers leads to misexpression of oncogenes that ultimately drive transformation. This review attempts to provide a basic understanding of enhancers and their role in transcriptional regulation, with a focus on normal and malignant hematopoiesis. We present examples of enhancers controlling master regulators of hematopoiesis and discuss the main mechanisms leading to enhancer dysregulation in leukemia and lymphoma.
Long-Term Clinical and Echocardiographic Outcomes Following the Ross Procedure
Authors: Maximiliaan L. Notenboom, Giovanni Melina, Kevin M. Veen, Fabio De Robertis, Giuditta Coppola, Paolo De Siena, Emiliano M. Navarra, Jullien Gaer, Michael E. K. Ibrahim, Ismail El-Hamamsy, Johanna J. M. Takkenberg, Magdi H. Yacoub
Journal: JAMA Cardiology (2023)

The Ross procedure as treatment for adults with aortic valve disease (AVD) has been the subject of renewed interest.